Inhibitory Effect of Caffeine on Carbachol-Induced Nonselective Cationic Current in Guinea-Pig Gastric Myocytes

  • Kim, Sung-Joon (Heart Research Institute, Seoul National University Medical Research Center) ;
  • Min, Kyung-Wan (Department of Physiology & Biophysics, Seoul National University College of Medicine) ;
  • Kim, Young-Chul (Department of Physiology & Biophysics, Seoul National University College of Medicine) ;
  • Lee, Sang-Jin (Department of Physiology, Chungbuk National University College of Medicine) ;
  • So, In-Suk (Department of Physiology & Biophysics, Seoul National University College of Medicine) ;
  • Kim, Ki-Whan (Department of Physiology & Biophysics, Seoul National University College of Medicine)
  • Published : 1998.06.21

Abstract

In gastrointestinal smooth muscle, muscarinic stimulation by carbachol (CCh) activates nonselective cation channel current ($I_{CCh}$) which is facilitated by intracellular [$Ca^{2+}$] increase. Caffeine is widely used in experiments to mobilize $Ca^{2+}$ from intracellular stores. This study shows a strong inhibitory effect of caffeine on $I_{CCh}$ in guinea-pig gastric myocyte. In this study, the underlying mechanism of the inhibitory effect of caffeine was investigated. $I_{CCh}$ was completely suppressed by the addition of caffeine (10 mM) to the superfusing solution. Inhibition of $I_{CCh}$ by caffeine was not related to the intracellular cAMP accumulation which was expected from the phosphodiesterase-inhibiting effect of caffeine. The blockade of $InsP_3-induced$ $Ca^{2+}$ release by heparin had no significant effects on the activation of $I_{CCh}$. When the same cationic current had been induced by intracellular dialysis of $GTP[{\gamma}S]$ in order to bypass the muscarinic receptor, the inhibitory effect of caffeine was significantly attenuated. The results of this study indicate that both intracellular signalling pathways for $I_{CCh}$, proximal and distal to G-protein activation, are suppressed by caffeine. A major inhibition was observed at the proximal level.

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